Chair and Moderator, Petros Grivas, MD, PhD, Shilpa Gupta, MD, and Gary D. Steinberg, MD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC activity titled “Breaking Down the Evidence in Bladder Cancer: Expert Perspectives and Practical Strategies on Immune, Targeted, and Antibody-Based Therapies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/2WcJp3n. CME/MOC credit will be available until December 31, 2022.

1. A Snapshot of Approved Therapies and
Ongoing Investigations in Urothelial Carcinoma
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/RPD40
DRUG/TARGET INDICATION DOSING
Approved for the treatment of adult pts with locally advanced UC or mUC who have previously
received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy in the
neoadjuvant/adjuvant, locally advanced, or metastatic setting
Approved for the treatment of pts with locally advanced UC or mUC who are ineligible for
cisplatin-containing chemotherapy and have received ≥1 prior line of therapy
Antibody–Drug Conjugates
Enfortumab vedotin6
Nectin-4
1.25 mg/kg (≤125 mg)
as IV infusion over
30 min on d 1, 8, and 15 of
a 28-d cycle until disease
progression or toxicity
Approved for the treatment of pts with locally advanced or metastatic disease
who are platinum ineligible
Approved for the treatment of pretreated pts with locally advanced UC or mUC who
progressed on prior platinum-based tx or relapsed within 1 y of perioperative
platinum-containing chemotherapy tx
Approved for the treatment of pts with BCG-unresponsive, high-risk NMIBC with CIS with
or without papillary tumors who are ineligible for or have elected not to undergo cystectomy
Pembrolizumab4
PD-1
200 mg every 3 wk
or 400 mg every 6 wk
240 mg every 2 wk
or 480 mg every 4 wk
Approved for the treatment of pretreated pts with locally advanced UC or mUC who
progressed on prior platinum-based tx or relapsed within 1 y of perioperative cisplatin tx
Approved for the adjuvant treatment of pts with UC who are at high risk of
recurrence after undergoing radical resection of UC
Nivolumab3
PD-1
Immune Checkpoint Inhibitors
Atezolizumab1
PD-L1
840 mg every 2 wk,
1,200 mg every 3 wk,
or 1,680 mg every 4 wk
Approved for the treatment of newly diagnosed pts with cisplatin-ineligible locally
advanced UC or mUC and PD-L1+ tumors (tumor-infiltrating ICs covering ≥5%
of the tumor area) or who are platinum ineligible
Companion diagnostic: Ventana PD-L1 (SP142) Assay
Approved for the treatment of pretreated pts with locally advanced UC or mUC who
progressed on prior platinum-based tx or relapsed within 1 y of perioperative
platinum-containing chemotherapy tx
Approved for maintenance treatment of pts with locally advanced UC
or mUC that has not progressed with first-line platinum-containing chemotherapy
Avelumab2
PD-L1
800 mg every 2 wk
Trop-2
10 mg/kg on d 1 and 8,
every 21 d until disease
progression or toxicity
Approved for the treatment of pts with locally advanced
UC or mUC who have had prior treatment with a PD-1 or PD-L1 inhibitor
and a platinum-containing chemotherapy regimen
Sacituzumab govitecan7
Approved for the treatment of pretreated pts with locally advanced UC or mUC who have
FGFR2 or FGFR3 genetic alterations and who progressed on prior platinum-based tx
or relapsed within 1 y of perioperative platinum-containing chemotherapy tx
Companion diagnostic: therascreen®
FGFR RGQ RT-PCR Kit
Erdafitinib5
FGFR
8 mg daily with
an increase
to 9 mg daily based on
PO4
levels and tolerability
at 14 to 21 d
FGFR Inhibitors
Therapeutic Targets, Indications, and Dosing Information

2. 1. Tecentriq (atezolizumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761034Orig1s042lbl.pdf. 2. Bavencio (avelumab) Prescribing Information.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761049s005lbl.pdf. 3. Opdivo (nivolumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125554s097lbledt.pdf.
4. Keytruda (pembrolizumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s113lbl.pdf. 5. Balversa (erdafitinib) Prescribing Information.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212018s001lbl.pdf. 6. Padcev (enfortumab vedotin-ejfv) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761137s006s008lbl.pdf.
7. Trodelvy (sacituzumab govitecan-hziy) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761115s009lbl.pdf. 8. www.clinicaltrials.gov.
Selected Ongoing Clinical Trials of Innovative Treatment
Options in Urothelial Carcinoma8
First-Line Metastatic Second-Line Metastatic
Bladder Preservation
Adjuvant MIBC
CheckMate -901 (NCT03036098) phase 3:
nivolumab + ipilimumab vs nivolumab
+ chemo vs chemo
NILE (NCT03682068) phase 3:
durvalumab + chemo ± tremelimumab
NCT04863885 phase 1/2:
ipilimumab + nivolumab combined with
sacituzumab govitecan for cisplatin-ineligible pts
vs chemo
NORSE (NCT03473743) phase 2:
erdafitinib + cetrelimab vs erdafitinib
THOR (NCT03390504) phase 3:
erdafitinib vs chemo vs pembrolizumab in pts
with selected FGFR mutations
TROPHY-U-01 (NCT03547973) phase 2:
sacituzumab govitecan
TROPiCS-04 (NCT04527991) phase 3:
sacituzumab govitecan vs chemo
NMIBC
Neoadjuvant
SunRISe-2 (NCT04658862) phase 3:
TAR-200 + cetrelimab vs gemcitabine/cisplatin
or RT
S1806 (NCT03775265) phase 3:
atezolizumab ± CRT in localized MIBC
AMBASSADOR (NCT03244384) phase 3:
pembrolizumab vs observation
IMvigor010 (NCT02450331) phase 3:
atezolizumab vs observation
ALBAN (NCT03799835) phase 3:
atezolizumab + BCG vs BCG
KEYNOTE-676 (NCT03711032) phase 3:
SunRISe-1 (NCT04640623) phase 2b:
TAR-200 + cetrelimab vs TAR-200 vs cetrelimab
pembrolizumab + BCG vs BCG
SWOG 1605 (NCT02844816) phase 2:
atezolizumab monotherapy
ENERGIZE (NCT03661320) phase 3:
nivolumab + chemo or nivolumab +
linrodostat (IDO1 inhibitor) + chemotherapy
→ immuno-oncology therapy after radical
cystectomy vs chemotherapy
KEYNOTE-866 (NCT03924856) phase 3:
Perioperative pembrolizumab +
neoadjuvant chemo vs perioperative placebo +
neoadjuvant chemo
NCT04209114 phase 3:
neoadjuvant and adjuvant nivolumab +
bempegaldesleukin vs nivolumab alone vs
SOC in pts with MIBC who are cisplatin ineligible
KEYNOTE-B15 (NCT04700124) phase 3:
pembrolizumab + enfortumab vedotin
NCT04241185 phase 3:
pembrolizumab + CRT in MIBC
A Snapshot of Approved Therapies and
Ongoing Investigations in Urothelial Carcinoma
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/RPD40

3. Guide to Managing Adverse Events Associated
With Therapies for Urothelial Carcinoma
Therapeutic Targets, Current Status/Indication, and Dosing Information
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/RPD40
• In general, checkpoint inhibitor therapy should be continued with close monitoring,
with the exception of some neurologic, hematologic, and cardiac toxicities
Minimal or no symptoms; diagnostic changes only
Grade 1
• Hold checkpoint inhibitor therapy for most grade 2 toxicities
• Consider resuming immunotherapy when symptoms and/or laboratory values
revert to grade 1 or lower
• Corticosteroids (initial dose of 0.5-1 mg/kg/d of prednisone or equivalent) may
be administered
Grade 3 toxicities
• Hold checkpoint inhibitor therapy
• Initiate high-dose corticosteroids (prednisone 1-2 mg/kg/d or methylprednisolone
IV 1-2 mg/kg/d)
• If symptoms do not improve with 48-72 hours of high-dose corticosteroids,
infliximab may be offered for some toxicities
• Taper corticosteroids over the course of at least 4-6 weeks
• When symptoms and/or laboratory values revert to grade 1 or lower, rechallenging
with immunotherapy may be offered; however, caution is advised, especially in
those patients with early-onset irAEs; dose adjustments are not recommended
Grade 4 toxicities
• In general, permanent discontinuation of checkpoint inhibitor therapy is warranted,
with the exception of endocrinopathies that have been controlled by hormone
replacement
Grade 2
Mild to moderate symptoms
Severe or life-threatening symptoms
Grades 3/4
Immune checkpoint inhibitors are associated with important clinical
benefits, but general immunologic enhancement can also lead to a
unique spectrum of immune-related adverse events (irAEs)1,2
irAEs are often diagnosed by
exclusion; other causes should
be ruled out (including AEs of
other therapies used), but
immunotherapy-related toxicity
should always be included
in the differential
There should be a high level of
suspicion that new symptoms
are treatment related; early
recognition, evaluation, and
treatment of irAEs plus patient
education are essential for
best outcomes
Depending on the severity
of irAEs, management may
require corticosteroid or
other immunosuppressive
treatment as well as
interruption or
discontinuation of therapy
If appropriate,
immunosuppressive
treatment is used; patients
generally recover from irAEs
How should irAEs be diagnosed?
What are the general recommendations
for irAE management?
What is the spectrum of potential irAEs?
Pancreatitis,
autoimmune diabetes
Colitis
Enteritis
Encephalitis, aseptic meningitis
Thyroiditis, hypothyroidism,
hyperthyroidism
Dry mouth, mucositis
Hypophysitis
Uveitis
Pneumonitis
Thrombocytopenia,
anemia
Hepatitis
Adrenal insufficiency
Nephritis
Vasculitis
Arthralgia
Neuropathy
Rash, vitiligo
Myocarditis
Any organ system can be affected; commonly occurring irAEs are pulmonary
(pneumonitis), dermatologic (rash, pruritus, blisters, ulcers, vitiligo),
gastrointestinal (diarrhea, enterocolitis, transaminitis, hepatitis, pancreatitis),
and endocrine (thyroiditis, hypophysitis, adrenal insufficiency)
Why do
irAEs occur?
“Taking the brakes off”
of the immune system can
help the body fight cancer,
but it can also lead to
toxicity from a
“supercharged”
immune system.

4. Safety Management for
FGFR Inhibitor Therapy8,9
Erdafitinib
 Mucositis, other oral toxicities
Oral
 Monitor for toxicities
 Refer to dermatology and
podiatry as needed
Skin and Nail
 Dietary phosphate may require
restriction
 Individualized dietary plan
from nutrition professional
 Consider adding a
non–calcium-containing
phosphate binder (eg,
sevelamer carbonate)
Dietary
FGF FGF
FGF
FGF
FGFR
HSPG
FGF FGF
FGFRL1
SEF
SPRY
FRS2
PLC-y
DAG STAT
GAB1
SOS
GRB2
RAS RAF
MEK
ERK MKP3
MKP1
AKT
PKC
PI3K
Nucleus
Transcription of
target genes
Cytoplasm
Extracellular
PIP2
P
P
P
P
P
P
P
P
P
P
P
P
IP3
Plasma membrane
Proliferation
and survival
Resistance to
anticancer agents
Neoangiogenesis
FGFR alterations:
Amplification (receptor
overexpression) or
mutation/translocation
(ligand-independent
signaling)
FGF ligand:
Amplification
(autocrine) or
ECM/stromal-
cell release
(paracrine)
FGFR in UC3,4
FGFR Signaling Pathway7
FGFR is altered in 15% to 20% of advanced UC.5
Mutated FGFR3 is present in 37% of upper-tract UC.6
FGFRs are a family of receptor tyrosine kinases that are upregulated in multiple different cancers
and are involved in tumor cell differentiation and proliferation, tumor angiogenesis, and tumor cell
survival; alterations in the FGFR gene, such as mutations and translocations, have been implicated
in the pathogenesis of UC
 Eye exams
 Withhold for any occurrence of
CSR or RPED
 Discontinue permanently if CSR/
RPED symptoms do not resolve
in 4 wk or if they escalate to grade 4
Ocular
Guide to Managing Adverse Events Associated
With Therapies for Urothelial Carcinoma
Therapeutic Targets, Current Status/Indication, and Dosing Information
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/RPD40

5. Sacituzumab Govitecan
Antibody–Drug Conjugates
Antibody–drug conjugates (ADCs) are molecules composed of an antibody chosen based on its ability to target a
tumor-specific protein linked to a cytotoxic payload or drug, enabling it to deliver a cytotoxic agent directly to the
targeted cells while minimizing toxicity to healthy cells10
Enfortumab Vedotin
Peripheral Neuropathy
 Generally resolves/remains at grade 1
Hyperglycemia
 Monitor blood glucose (patients with/at risk for
diabetes or hyperglycemia)
Maculopapular Diffuse Rash
 Topical steroids
 Antihistamines
 Dose reductions/delays
 Systemic corticosteroids (special cases)
Diarrhea
 Educate patients
 Hydration with electrolytes
 Anti-diarrheal medications
 Best supportive care
Safety Management for Antibody–Drug
Conjugate Therapy11-13
1Binds to
antigen
2Complex is internalized
and traffics to lysosome
3Payload is released
and causes cell death
Neutropenia
 Consider growth factor support
 Dose reduction or hold
Sacituzumab Govitecan
Enfortumab Vedotin
Target: Nectin-4, a type 1 transmembrane cell
adhesion molecule overexpressed in epithelial cancers
Linker: Protease cleavable
Payload: MMAE
Target: Trop-2, an epithelial cell-surface glycoprotein
highly expressed in muscle-invasive disease
Linker: Hydrolysable
Payload: SN-38, the active metabolite of irinotecan
1. Postow MA et al. N Engl J Med. 2018;378:158-168. 2. Brahmer JR et al. J Clin Oncol. 2018;36:1714-1768. 3. https://tcga-data.nci.nih.gov/docs/publications/tcga.
4. Knowles MA et al. Nat Rev Cancer. 2015;15:25-41. 5. Rodriguez-Vida A et al. J Hematol Oncol. 2015;8:119. 6. Li Q et al. Curr Urol Rep. 2016;17:12. 7. Touat M et al. Clin Cancer Res. 2015;21:2684-2694.
8. Loriot Y et al. N Engl J Med. 2019;381:338-348. 9. Balversa (erdafitinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212018s001lbl.pdf. 10. Parslow AC et al.
Biomedicines. 2016;4:14. 11. Rosenberg JE et al. J Clin Oncol. 2019;37:2592-2600. 12. Loriot Y et al. Ann Oncol. 2020;31(suppl 4)s1142-s1215. 13. Petrylak DP et al. J Clin Oncol. 2020;38(suppl): Abstract 5027.
Guide to Managing Adverse Events Associated
With Therapies for Urothelial Carcinoma
Therapeutic Targets, Current Status/Indication, and Dosing Information
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/RPD40